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Adv Healthc Mater. 2016 Dec;5(24):3157-3164. doi: 10.1002/adhm.201600797. Epub 2016 Nov 8.

StarPEG-Heparin Hydrogels to Protect and Sustainably Deliver IL-4.

Author information

1
Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), Hohe Str. 6, 01069, Dresden, Germany.
2
Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Fetscherstraße 105, 01307, Dresden, Germany.

Abstract

A major limitation for the therapeutic applications of cytokines is their short half-life time. Glycosaminoglycans (GAGs), known to complex and stabilize cytokines in vivo, are therefore used to form 3D-biohybrid polymer networks capable of aiding the effective administration of Interleukin-4, a key regulator of the inflammatory response. Mimicking the in vivo situation of a protease-rich inflammatory milieu, star-shaped poly(ethylene glycol) (starPEG)-heparin hydrogels and starPEG reference hydrogels without heparin are loaded with Interleukin-4 and subsequently exposed to trypsin as a model protease. Heparin-containing hydrogels retain significantly higher amounts of the Interleukin-4 protein thus exhibiting a significantly higher specific activity than the heparin-free controls. StarPEG-heparin hydrogels are furthermore shown to enable a sustained delivery of the cytokine for time periods of more than two weeks. Primary murine macrophages adopt a wound healing supporting (M2) phenotype when conditioned with Interleukin-4 releasing starPEG-heparin hydrogels. The reported results suggest that GAG-based hydrogels offer valuable options for the effective administration of cytokines in protease-rich proinflammatory milieus such as chronic wounds of diabetic patients.

KEYWORDS:

Interleukin-4; biohybrid hydrogels; cytokines; glycosaminoglycan; stabilization; sustained release

PMID:
27860466
DOI:
10.1002/adhm.201600797
[Indexed for MEDLINE]

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